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Microbicides for sexually transmitted diseases



A major effort is currently underway to develop topical microbicides for sexually transmitted diseases, that might be applied to condoms or directly to the genitals to block sexually transmitted diseases (STDs), such as HIV. It is hoped that these products could be produced inexpensively and distributed freely worldwide. A successful microbicide product would be of particular benefit to women in countries where culturally-accepted, abusive relationships make it difficult or impossible for women to negotiate condom use.

Additional recommended knowledge

Contents

Nonoxynol-9

Early in the HIV/AIDS epidemic, it was discovered that a commonly-used spermicide called nonoxynol-9 can block the replication of HIV in laboratory tests. For more than a decade, public health professionals recommended nonoxynol-9 for use as a topical microbicide, and many condom and sexual lubricant brands incorporated nonoxynol-9 for this purpose. However, subsequent clinical research showed that nonoxynol-9's irritating detergent effects can result in the formation of erosions or sores in the vagina or rectum. Such sores are now believed to serve as sites of entry for HIV and other STDs and there is substantial clinical evidence suggesting that regular use of nonoxynol-9 actually increases the risk of HIV infection. Consequently, there is now a broad consensus in the public health community that nonoxynol-9 should NOT be used as a topical microbicide.[1]

Current progress

Despite the false start with nonoxynol-9, there has been significant recent progress toward the development of safe and effective topical microbicides. Several different gel formulations, including Carraguard, PRO 2000, and BufferGel are currently undergoing testing in phase III clinical efficacy trials and about two dozen other products are in various phases of development [2][3]. In most cases, it is hoped that the gels will block the transmission of HIV, as well as other STDs, such as human papillomaviruses (HPVs) and herpes simplex viruses (HSVs). For example, carrageenan, the active ingredient in Carraguard, has been shown to block the replication of all three virus types in laboratory studies. Interestingly, carrageenan is already in use as a gelling agent in some over the counter personal lubricant products, such as Bioglide, Divine, and Oceanus Carrageenan brands. Viva Gel is a particularly unique microbicide in that its active ingredient is a nanoscale dendrimer and 85-100% effective at stopping the transmission of both HIV and genital herpes in macaque monkies.[clarify] The NIH and NIAID have awarded grants totaling $25.7 million for VivaGel's continued development and testing. VivaGel is also being evaluated for use in condoms by a leading manufacturer.

Further information: Carrageenan#Sexual lubricant and microbicide

Mechanisms of action

Detergent microbicides, such as nonoxynol-9, sodium dodecyl sulfate and Savvy, can function by disrupting the outer coat or lipid membrane of viruses and bacteria. Since detergent microbides also tend to kill cells and impair the barrier function of healthy mucosal surfaces, they are less preferred.

Healthy vaginal pH is typically quite acidic (pH 4). However, the alkaline pH of semen can effectively neutralize vaginal pH. It is hoped that candidate microbicides such as Buffergel, lime juice [4] and preparations of live Lactobacillus baceria might act by promoting acidic vaginal pH, which can in turn inactivate pathogenic viruses and bacteria.

Another microbicide class is embodied by Carraguard and PRO 2000, which are expected to function by preventing microbes from binding to the surface of cells. Carrageenan chemically resembles cellular heparan sulfate polysaccharides, which many microbes utilize for initial attachment to cell surfaces. Thus, carrageenan and other microbicides of its class act as decoys for virus binding.

Drugs that specifically target the molecular features of HIV are also being investigated as topical microbicides. In some instances, HIV drugs that cannot be absorbed orally are under consideration, since they could conceivably function when applied topically.

Ultimately, successful topical microbicides may simultaneously employ multiple modes of action.

Microbicide formulations

Most of the first generation microbicides undergoing development are formulated as semi-solid systems, such as gels or creams, and are designed to be applied to the vagina via an applicator before every act of intercourse. Vaginal ring devices are also being developed that have the potential to provide long-term controlled release of microbicides.

Social factors

Condoms are a highly effective method for blocking the transmission of most STDs (with HPVs being a notable exception). However a variety of social factors, including the sexual disempowerment of women in many cultures, tend to limit the feasibility of condom use. Thus, topical microbicides might provide a useful woman-controlled alternative to condoms, particularly if the microbicides could be applied without the knowledge of male partners.

Many sub-Saharan African cultures view vaginal lubrication as undesirable [5][6]. Since all topical microbicides currently under development function as lubricants, such dry sex traditions may pose a major barrier to the implementation of topical microbicide programs in the areas most severely affected by the HIV/AIDS epidemic.

Most individuals who engage in anal sex routinely use some form of lubricant product. The fact that substantial numbers of gay men in developed countries continue to use lubricants containing nonoxynol-9 demonstrates that they are generally aware of the concept of topical microbicides and might rapidly adopt a clinically successful rectal microbicide product [7]. Unfortunately, the development of rectal microbicides is not as advanced as that of vaginal microbicides. Several biological differences (such as the rectum's thinner epithelium, greater surface area, lower degree of elasticity) mean that a microbicide that is effective when applied vaginally might not be effective when applied rectally. Therefore, increased investment in rectal microbicide research is needed.

References

  1. ^ WHO Microbicide overview
  2. ^ Alliance for Microbicide Development clinical pipeline database
  3. ^ Global Campaign for Microbicides Product Pipeline List
  4. ^ Bitter fruit: Another idea for stopping AIDS falls flat. The Economist, April 27, 2006
  5. ^ Hyena, H. (1999) "Dry sex" worsens AIDS numbers in southern Africa Salon, Dec 10.
  6. ^ Myer, L. et al. (2005) Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms Lancet Infectious Diseases 5(12):786. PMID 16310150
  7. ^ Carballo-Diéguez, A., et al. (2006) Awareness and Attitudes Regarding Microbicides and Nonoxynol-9 use in a Probability Sample of Gay Men AIDS and Behavior PMID 16775772

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Microbicides_for_sexually_transmitted_diseases". A list of authors is available in Wikipedia.
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